Structures and biofilm inhibition activities of brominated furanones for Escherichia coli and Pseudomonas aeruginosa

Abstract

A series of brominated furanones (BFs) with closely related structures was synthesized and evaluated for biofilm inhibition activity against Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa). The structure–activity relationships (SARs) indicated that methyl substituent on the furanone ring and on the exocyclic vinyl double bond is important for relieving the inhibitory effect of these molecules on the growth of both E. coli and P. aeruginosa. To explore the mechanism of BFs to inhibit E. coli biofilm, the biofilm inhibition activity of BFs in wild type E. coli and its sdiA knockout mutant (ΔsdiA) was compared, which is proposed to encode the receptor for BFs. We found that ΔsdiA caused ∼2 fold reduction in biofilm inhibition activity of BFs compared with that of the wild type E. coli. To explore the effect of BFs on quorum sensing of P. aeruginosa, we use reporter gene assays that examine the effect of BFs on the las and rhl quorum sensing systems. Interestingly, while BFs exhibited antagonistic activities to LasR protein in the las system, these molecules showed agonistic activity to RhlR protein in the rhl system. Furthermore, one BF molecule, BF15, inhibited the production of the virulence factor elastase B without significant inhibition of biofilm formation. As the growth and biofilm inhibition activity of BFs are closely related to their structural details, this class of molecules bears potential for further design of non-microbicidal agents to control bacterial biofilm formation.